Influence of Physical Activity during Pregnancy on Neonatal Complications: Systematic Review and Meta-Analysis

Newborn hospitalisations after delivery are indicators of poor neonatal health with potential risks of future diseases for children. Interventions to promote a healthy environment have been used during pregnancy, with physical activity as a principal element. A systematic review and meta-analyses were performed to evaluate the effect of physical activity during pregnancy on neonatal intensive care unit (NICU) admissions and Apgar 1 and 5 scores (Registration No.: CRD42022372493). Fifty studies (11,492 pregnant women) were included. There were significantly different rates of NICU admissions between groups (RR = 0.76, 95% CI = 0.62, 0.93; Z = 2.65, p = 0.008; I2 = 0%, and Pheterogeneity = 0.78), and significant differences in Apgar 1 (Z = 2.04; p = 0.04) (MD = 0.08, 95% CI = 0.00, 0.17, I2 = 65%, Pheterogeneity = 0.00001) and Apgar 5 (Z = 3.15; p = 0.002) (MD = 0.09, 95% CI = 0.04, 0.15, I2 = 80%, and Pheterogeneity = 0.00001), favouring intervention groups. Physical activity during pregnancy could help to reduce the risk of NICU admissions that are related to neonatal complications.


Introduction
Evidence of poor neonatal health includes the occurrence of newborn hospitalisations after delivery [1].The consequences of an unhealthy pregnancy and associated conditions, such as gestational diabetes or hypertension, translate into short-term risks for the newborn that result in long-term consequences for the infant [2].Furthermore, hypothalamicpituitary-adrenal activation throughout pregnancy is linked to fetal programming [3].
The admission to the neonatal intensive care unit (NICU) after delivery is associated with neonates born prematurely and/or growth-restricted (i.e., small-for-gestational age and intrauterine growth restriction).In addition to IUGR and premature delivery, NICU admissions are also related to low Apgar scores, excess neonatal body fat (i.e., high body weight, ponderal index, and BMI), low cord blood pH, hyperbilirubinemia, neonatal hypoglycemia (serum glucose concentration < 40 mg/dL), shoulder dystocia, and brachial plexus injury [4][5][6].Other common complications of neonates in the NICU are hyperglycemia (serum glucose concentration > 150 mg/dL), as well as respiratory and metabolic disorders in infancy [7,8].Additionally, neonates with hyperglycemia are often born with extremes in birth weight, either too small or too large [1].
Further, these fetal and neonatal complications, which lead to NICU admission, are associated with long-term health problems [9,10].For example, short-term neonatal complications soon after delivery are associated with negative long-term effects on childhood development (e.g., low neurodevelopment scores) [11] and health across the lifespan (e.g., obesity, diabetes, and cardiovascular disease) [12,13].Furthermore, high anxiety in mothers, autonomously of the baby's birth situation and the moment of evaluation, comprises a possible risk factor for the child's development, even in the fetal period [14].
Conversely, physical activity during pregnancy, meeting the international recommendations of 150 min of moderate physical activity every week, benefits the fetal-placentalmaternal interface [15].Therefore, access of pregnant women to physical activity is vital for promoting the short-and long-term health of the child.However, whether maternal physical activity during pregnancy impacts the incidence of neonatal complications is not known [16][17][18].
Despite many known benefits for the mother, prenatal exercise was previously thought to increase the odds of neonatal complications, such as preterm birth and intrauterine growth restriction [12].Conversely, studies show that admission to the NICU admission for infants is less common in women who exercise during pregnancy [5].
Furthermore, research has shown that physical activity (PA) during pregnancy could have a positive effect on neonatal and maternal outcomes, which is closely linked to NICU admissions.For instance, PA during pregnancy decreases gestational weight gain and the risk of gestational diabetes while increasing gestational age and Apgar scores [19,20].
PA is seen as an enhancer of maternal and fetal health, improving these interrelated health outcomes.Moreover, the association between the time spent in physical activity and symptoms of depression and anxiety in the antenatal period was previously demonstrated [21].Unfortunately, only 20% of the world population meets the international guidelines for exercise during pregnancy [22].Further, the worldwide prevalence of pregnant women who do not meet the ACOG physical activity recommendations is steadily rising [23].Since the influence of PA during pregnancy on neonatal outcomes remains unclear [24], it is necessary to review the effect of maternal physical activity during pregnancy on neonatal health.Therefore, the purpose of this review is to examine the correlations between physical activity during pregnancy and NICU admission and Apgar scores after delivery.

Materials and Methods
This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P.R.I.S.M.A.) guidelines.The protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) (CRD42022372493).

Eligibility Criteria
The PICOS (population, intervention, comparison, outcome, and study design) strategy was used to guide this review with meta-analysis [25].

Population
The population of interest comprised of healthy pregnant women aged between 18 and 45 years, regardless of their gestational age at the time of study admission.Participants had no contraindications for physical activity or exercise, as defined by the American College of Obstetricians and Gynecologists (ACOG) guidelines [26].

Intervention
Interventions that include any format of physical activity or physical exercise during pregnancy (individual/group), (autonomous/supervised), (face-to-face/online), and co-interventions: exercise combined with other interventions (e.g., diet intervention or behavioral intervention) were evaluated.The intervention investigated in each study must be related to objective or subjective measures of intensity, duration, volume, or type of exercise.

Comparison
In this case, the comparison group was the control or non-intervention group of the selected studies.This was based on not practicing routine physical activity during pregnancy, following only standard medical care.

Variable
The primary study variable was the NICU admissions record.The studies had to contain at least the primary study variable (NICU admission) to be included in the analysis; if a study failed this step, then it was registered as a potentially relevant secondary variable for analysis.The secondary variable was Apgar 1 and Apgar 5 scores in quantitative and qualitative format.

Study Design
Studies that were randomized clinical trial interventions were selected.Thus, studies with non-randomized interventions, observational studies, some type of review (narrative, systematic, or systematic review with meta-analysis), and qualitative research were excluded.

Data Sources
An exhaustive and comprehensive search was completed in the following databases: MEDLINE, Scopus, Sport Discus, Academic Search Premier, ERIC, OpenDissertations, Clinicaltrial.gov,Cochrane Database of Systematic Reviews, and Web of Science through the portal of the Universidad Politécnica de Madrid.
The search was conducted between October 2022 and November 2022.The same article selection criteria were used for all the databases to guarantee equality.In the selection process, articles written in Spanish and English published between 2010 and 2023 were considered for the search.Bibliographic references of selected studies were reviewed to identify other potential studies that might have been missed by the electronic keyword search.

Selection and Data Extraction
Figure 1 shows the selection process that was followed for the reviewed articles.Two investigators independently screened the titles and abstracts identified from the electronic searches to select potentially relevant studies based on the inclusion criteria.
Abstracts were identified and passed an initial screen; then, full-text searches were performed post hoc.Full texts were reviewed separately for priority results for data extraction.In addition, relevant data were extracted from 50 studies to ensure that no valuable information was missed.
For studies in which one of the authors recommended exclusion, both authors reached a consensus to make a final decision on inclusion or not.In situations of absolute disagreement, a third author provided their assessment of study inclusion or not.One person extracted the data to complete the tables, which were independently verified by a content expert to facilitate further analysis.Abstracts were identified and passed an initial screen; then, full-text searches were performed post hoc.Full texts were reviewed separately for priority results for data extraction.In addition, relevant data were extracted from 50 studies to ensure that no valuable information was missed.
For studies in which one of the authors recommended exclusion, both authors reached a consensus to make a final decision on inclusion or not.In situations of absolute disagreement, a third author provided their assessment of study inclusion or not.One person extracted the data to complete the tables, which were independently verified by a content expert to facilitate further analysis.
In this review, data were extracted from tables or from the text using simple methods, excluding articles that presented data in figure form.This way, the reliability and authenticity of the data are guaranteed.Extracted data included study characteristics (e.g., author's last name and year, country), article type (randomized clinical trial-RCT), sample size and group differences, intervention/exposure (exercise prescribed and/or measured), including frequency, intensity, time, and type, supervision of the intervention, duration, and adherence to the intervention).Primary and secondary variable(s) were analysed, and co-intervention associations, if any, were also considered (Table 1).

Evidence Quality Assessment
To assess the quality of evidence for each study design and main outcome, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used.This framework provided a standardized and comprehensive approach to assess the strength of evidence across multiple studies [27].There were 50 randomized clinical trials rated as high included in this meta-analysis.

Risk of Bias Assessment
The Cochrane Handbook was used to assess the risk of bias (Figure 2).Potential sources of bias were assessed in all studies.These sources included selection bias In this review, data were extracted from tables or from the text using simple methods, excluding articles that presented data in figure form.This way, the reliability and authenticity of the data are guaranteed.Extracted data included study characteristics (e.g., author's last name and year, country), article type (randomized clinical trial-RCT), sample size and group differences, intervention/exposure (exercise prescribed and/or measured), including frequency, intensity, time, and type, supervision of the intervention, duration, and adherence to the intervention).Primary and secondary variable(s) were analysed, and co-intervention associations, if any, were also considered (Table 1).

Evidence Quality Assessment
To assess the quality of evidence for each study design and main outcome, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used.This framework provided a standardized and comprehensive approach to assess the strength of evidence across multiple studies [27].There were 50 randomized clinical trials rated as high included in this meta-analysis.

Risk of Bias Assessment
The Cochrane Handbook was used to assess the risk of bias (Figure 2).Potential sources of bias were assessed in all studies.These sources included selection bias (inadequate randomisation procedures for RCTs/interventions), performance bias (intervention compliance for RCTs/interventions), detection bias (faulty outcome measurement), attrition bias (incomplete follow-up and high loss of participants during follow-up), and reporting bias (incomplete or selective reporting of results) [28].Overall, the quality of the evidence ranged from low to high.Although the risk of bias was detected, it was chosen not to exclude any study from the analyses.

Publication Bias Assessment
To assess potential publication bias in each developed meta-analysis, the Egger regression test was employed due to its enhanced sensitivity in detecting publication bias under conditions of weak or moderate heterogeneity.Typically, this test yields a metric indicating significant publication bias when p < 0.1 [29].

Statistical Analysis
Statistical analyses were performed using RevMan (version 5.4) software.NICU admission and Apgar 1 > 7 and Apgar 5 > 7 were expressed as dichotomous categorical outcomes (Yes/No); the number of NICU admissions and Apgar 1 > 7 and Apgar 5 > 7 events in the intervention and control groups and their relative risk (RR) were recorded.A random-effects model was used to calculate the total sum of the RR [30].To establish the balanced mean in the dichotomous analysis, a weighting system was used that considered the sample size or number of events reported by each study.This weighting system accounts for the different levels of information provided by each study, which allows a more precise representation of the general data.The I 2 statistic was used to measure the degree of heterogeneity of the results.This metric provides information about the proportion of variability in the observed intervention effect between studies that is attributed to heterogeneity rather than chance.The I 2 statistic was interpreted using established thresholds: 25% for low heterogeneity, 50% for moderate heterogeneity, and >75% for high heterogeneity [30].For continuous outcomes, Apgar 1 and Apgar 5 scores, obtained through medical records of analysed articles, the standardized mean difference (SMD) was used.The overall confidence interval (CI) was calculated using the standardized mean difference [30].

Study Selection
The PRISMA diagram presenting the search results along with explanations for the study exclusion is shown in Figure 1.
Specifically, the exercise interventions were completed in a range of low to moderate intensity, with a frequency varying from 1 to 7 days a week and a duration between 10 to 60 min per session.The interventions vary in their timing across gestation, with interventions throughout the pregnancy (week 8 to week 39) and other interventions during each trimester (week 8 to week 39).The type of exercise includes aerobics, resistance/muscular strength training, stretching, pelvic floor muscle training, balance, coordination, flexibility, or Pilates and yoga programs.Additional details are shown in Table 1.
Regarding the secondary variables, it was found maternal outcomes that include demographic characteristics (Age, parity, race, marital status, education, gravidity, maternal height and weight, hypertension, blood pressure, gestational diabetes, maternal fitness, psychological well-being, physical activity, and quality of life) and prenatal outcomes (gestational weight gain, gestational length of delivery, excessive weight gain, preeclampsia, mode of delivery, duration of labour, analgesia requirement during labour, episiotomy, and perineal tears).On the other hand, neonatal outcomes such as birth weight, low birth weight, small-for-gestational age, fetal growth restriction, fetal distress, preterm birth, placental weight, or neonatal death and other morbidities were recorded.NICU admission and Apgar Score results are presented in the following paragraphs.

Effect of Physical Activity during Pregnancy on Apgar 1 > 7
In this qualitative analysis, a total of six randomized clinical trial studies were incorporated [40,48,51,52,55,57].No statistical significance was found between physical activity during pregnancy and the occurrence of Apgar 1 > 7 (RR = 1.03, 95% CI = 0.98, 1.08; Z = 1.18, p = 0.24; I 2 = 63%, Pheterogeneity = 0.02).The quantitative assessment of publication bias risk in the analysed articles indicated the absence of potential publication bias (p = 0.1) in this analysis.Figure 4 illustrates the forest plot corresponding to the conducted meta-analysis.

Effect of Physical Activity during Pregnancy on Apgar 1 > 7
In this qualitative analysis, a total of six randomized clinical trial studies were incorporated [40,48,51,52,55,57].No statistical significance was found between physical activity during pregnancy and the occurrence of Apgar 1 > 7 (RR = 1.03, 95% CI = 0.98, 1.08; Z = 1.18, p = 0.24; I 2 = 63%, P heterogeneity = 0.02).The quantitative assessment of publication bias risk in the analysed articles indicated the absence of potential publication bias (p = 0.1) in this analysis.Figure 4 illustrates the forest plot corresponding to the conducted meta-analysis.

Effect of Physical Activity during Pregnancy on Apgar 1 > 7
In this qualitative analysis, a total of six randomized clinical trial studies were incorporated [40,48,51,52,55,57].No statistical significance was found between physical activity during pregnancy and the occurrence of Apgar 1 > 7 (RR = 1.03, 95% CI = 0.98, 1.08; Z = 1.18, p = 0.24; I 2 = 63%, Pheterogeneity = 0.02).The quantitative assessment of publication bias risk in the analysed articles indicated the absence of potential publication bias (p = 0.1) in this analysis.Figure 4 illustrates the forest plot corresponding to the conducted meta-analysis.

Effect of Physical Activity during Pregnancy on other Neonatal Outcomes
In addition, an attempt was made to analyse data from other present neonatal birth outcomes, such as shoulder dystocia, brachial plexus injury, cord blood pH, hyperbilirubinemia, or neonatal hypoglycaemia, but the analyses could not be performed due to their limited occurrence.

Discussion
According to our understanding, the present study is the first systematic review of the influence of regular physical activity on NICU admissions and Apgar scores, delving into 50 quality articles on said theme.This work provides a key contribution to support the idea that physical activity during pregnancy helps prevent admissions to the neonatal intensive care unit and improves APGAR scores.At this point, it was observed that maintaining physical activity during pregnancy increases the probability of having better postnatal outcomes and preventing complications.
Our systematic review with meta-analysis examined the relationship between systematic and regular physical activity during pregnancy and NICU admission and observed consistent findings compared to previous studies [80,81].In this sense, lower NICU admissions have been found in the group of women who maintain regular physical activity; these results are consistent with previous studies that suggest newborns of women

Effect of Physical Activity during Pregnancy on other Neonatal Outcomes
In addition, an attempt was made to analyse data from other present neonatal birth outcomes, such as shoulder dystocia, brachial plexus injury, cord blood pH, hyperbilirubinemia, or neonatal hypoglycaemia, but the analyses could not be performed due to their limited occurrence.

Discussion
According to our understanding, the present study is the first systematic review of the influence of regular physical activity on NICU admissions and Apgar scores, delving into 50 quality articles on said theme.This work provides a key contribution to support the idea that physical activity during pregnancy helps prevent admissions to the neonatal intensive care unit and improves APGAR scores.At this point, it was observed that maintaining physical activity during pregnancy increases the probability of having better postnatal outcomes and preventing complications.
Our systematic review with meta-analysis examined the relationship between systematic and regular physical activity during pregnancy and NICU admission and observed consistent findings compared to previous studies [80,81].In this sense, lower NICU admissions have been found in the group of women who maintain regular physical activity; these results are consistent with previous studies that suggest newborns of women who exercised while pregnant were healthier.In this way, fewer neonatal complications are associated with babies who do not go to the NICU [5].
Up to this point, previous scientific evidence does not know whether maternal physical activity during pregnancy affects the incidence of neonatal complications [16][17][18].What is known is that neonatal complications are associated with long-term negative effects on child development (e.g., neurodevelopmental scores) and lifelong health (e.g., obesity, diabetes, or cardiovascular diseases) [11][12][13].Research has shown that physical activity during pregnancy could have a positive effect on neonatal outcomes, such as Apgar scores [19]; thus, encouraging physical activity during pregnancy by clinicians and inpatient institutions is vital to prevent delivery complications.
Consequently, pregnant women should lead a healthy lifestyle throughout pregnancy.To do this, study findings must be carefully and collectively weighed to formulate unique decisions for each woman's situation.Additionally, more research is required to determine the lowest and maximum effects of physical activity levels throughout the entire pregnancy.
On the other hand, when it comes to physical exercise programs with pregnant women, PA is seen as an enhancer of maternal and fetal health, improving health parameters that may be interrelated [82].For this review, studies were found with different objectives, methodologies, and interventions, although the central axis of these programs was strength and aerobic exercises.The plurality in the typology of interventions makes generalisation and firm extrapolation of results difficult.However, interventions with physical exercise as an agent to mitigate these negative effects are an urgent research approach.
It is important to consider that this systematic review and meta-analysis has several limitations in its approach, such as heterogeneity, publication bias, or the quality of the evidence.While the findings of this study provide support for engaging in moderate physical activity during pregnancy, seemingly without posing a risk of neonatal complications, it is imperative to approach these results with considerable caution, recognizing the imperative for further research in this area.To date, this is the first in-depth systematic review of the variables analysed.Therefore, high-quality studies are required to shed additional light on the relationship between exercise during pregnancy in terms of several fetal parameters.
For this reason, it is crucial to emphasize the value of exercise during pregnancy to reverse the physiological effects of physical inactivity in new generations.These findings can encourage pregnant women to maintain or achieve a minimum level of daily activity to improve neonatal health outcomes.

Conclusions
The quality of evidence from randomized controlled trials showed that prenatal physical activity could reduce the risk for NICU admissions compared with control groups.Additionally, PA during pregnancy contributes to better Apgar 1 and 5 scores among healthy pregnant women.

Figure 1 .
Figure 1.Flow chart of the review process.

Figure 1 .
Figure 1.Flow chart of the review process.
NoRef: references.Author: last name.Year: year of study.Country: the country where the article has been completed.Type: type of article; N: total number of women analysed.GI: number of women analysed in the intervention group.GC: number of women analysed in the control group.Freq: weekly frequency of exercise sessions.Intens: type of intensity.Tp: program time.Type: type of exercise performed.Superv.classes: whether or not there was supervision.Duration: minutes of each session.Adh.: adherence of the participants to the intervention (%).Main variables and secondary variables: the same as before but secondary.Wk: week.